Semaglutide (Wegovy®) for weight management

Stigma surrounding obesity, subconscious bias among healthcare providers, personal health beliefs, and prior negative experiences with healthcare professionals can make weight management discussions challenging for patients to initiate and clinicians to navigate.

Obesity is best understood as a chronic condition driven by biological, genetic, and socio-structural-environmental factors.  Many individuals, including health professionals, see obesity as a willpower issue, as opposed to a complex chronic condition driven by altered physiology.  

Understanding a patient’s journey with weight loss efforts can offer valuable insight.  A helpful conversation prompt to explore this is:

“Tell me about your efforts with trying to lose weight in the past.”

Individualised lifestyle intervention is the key component of weight management for all patients. This includes:

• meal planning and dietetic education
• physical activity/movement
• behavioural modification.  

However, these interventions on their own may not be sufficient to achieve or sustain long-term weight loss.  

Pharmacotherapy can support patients in maintaining lifestyle changes, reducing obesity-related health risks, and improving quality of life. Pharmacotherapy can also play a role in preventing obesity-related complications and as an adjunct to cardiovascular risk modification in overweight individuals.

Currently available obesity management medications (OMMs) are classified into three groups by mechanism of action¹:

1. Glucagon-like peptide-1 (GLP-1) receptor agonists: nutrient-stimulated hormone-based medications (e.g. semaglutide, liraglutide) which mimic endogenous entero-pancreatic hormones that regulate appetite and energy balance via the gut–brain axis.
2. Intra-gastrointestinal medications (e.g. orlistat):  reduce fat absorption.
3. Centrally acting medications (e.g., phentermine, naltrexone-bupropion): target the central nervous system to suppress appetite (phentermine) or reduce food reward and cravings (naltrexone/bupropion).

Wegovy and Ozempic contain the same active ingredient, semaglutide.  

Ozempic is indicated for the management of type 2 diabetes, while Wegovy is indicated for weight management.  

• Prescribers must select the correct formulation.  
• Maximum doses differ (Wegovy 2.4mg versus Ozempic 1.0mg).
• Semaglutide is a long-acting GLP-1 receptor agonist self-administered via once-weekly subcutaneous injection.

GLP-1 is a natural hormone that regulates glycaemic control. It is released from the gut in response to the detection of ingested nutrients and acts to enhance insulin release, reduce hunger and slow gastric emptying.  

Semaglutide shares 94% structural similarity with human GLP-1 and mimics its actions. The key difference between semaglutide and native GLP-1 is the half-life, which is a few minutes for the native hormone and approximately one week for semaglutide.

The net clinical effect of semglutide is a reduction in overall energy intake through enhanced satiety and perceived control of eating.  Patients may experience improved control of eating habits and reduced preference for foods high in fat content. This supports adherence to dietary and lifestyle modifications.

In addition to its glycaemic and satiety effects, semaglutide independently reduces cardiovascular risk. The mechanisms behind this are unclear but likely relate to endothelial function or reduced inflammation. 

Wegovy is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management (including weight loss and weight maintenance) in adults with an initial Body Mass Index (BMI) of:

• ≥30 kg/m², or
• ≥27 kg/m² with at least one weight-related comorbidity:
  • Hypertension
  • Dyslipidaemia
  • Obstructive sleep apnoea
  • Pre-diabetes
  • Non-alcoholic fatty liver disease
  • Polycystic Ovary Syndrome.

Wegovy is indicated (but not currently funded) for cardiovascular risk reduction as an adjunct to standard of care therapy in individuals with established cardiovascular disease and BMI ≥27 kg/m², without diabetes mellitus.

Treatment with semaglutide in the SELECT trial resulted in a significant risk reduction (20%) in the 3-component MACE outcome (defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) compared with placebo.  

Adverse events leading to permanent discontinuation of the medication occurred in 16.6% in the semaglutide group and 8.2% in the placebo group (P<0.001).²

Wegovy is approved as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adolescents aged ≥12 years who meet all of the following:

• Initial obesity (BMI ≥ 95th percentile on sex- and age-specific CDC BMI growth charts), and
• Body weight > 60 kg.

Clear expectations should be set with the patient at the outset³.

In the STEP-1 trial, mean weight loss was 14.9% at 68 weeks, compared with 2.4% in the placebo group⁴.  This correlated with an average weight loss of 15.3kg, compared with 2.6kg in the placebo group.  Around half of the participants lost 15% body weight, and a third lost 20% body weight. 

To achieve this result, participants were advised to follow a daily 500 kcal energy deficit based on estimated energy expenditure at the time of randomisation, and to engage in at least 150 minutes of physical activity per week (eg. walking). It must be emphasised that these medications do not cause weight loss on their own. Lifestyle change remains the cornerstone of weight management, with semaglutide and related medications serving to help with adherence to lifestyle change.

Goals should be holistic, and do not need to focus on weight management alone. Patients should be advised to set “non-scales goals” – outcomes that are important to them beyond a change in a number on a scale (for example: being able to walk up a flight of stairs without stopping; having their periods return; being able to stop taking insulin etc).  

Broader health-related aspects should be considered, including:

• Positive dietary changes.
• Increased movement/physical activity.
• How they are feeling overall.

Conversation prompts may include:

"What kind of changes would you like to prioritise first?"

"What are the most important goals you could set regarding your weight?"

Wegovy is administered via subcutaneous injection using the FlexTouch® pen. The pen is available in pre-mixed doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 mg, with each pre-filled pen containing four doses⁵.

Wegovy is administered once weekly at any time of day, with or without meals.

It is injected subcutaneously into the abdomen, thigh, or upper arm. The injection site should be rotated.

Wegovy has similar storage rules to insulin: pens should not be exposed to extremes of temperature and should be stored in the fridge until opened.
 

• Week 1-4: 0.25mg
• Week 5-8: 0.5mg
• Week 9-12: 1mg
• Week 13-16: 1.7mg
• Maintenance dose: 2.4mg.

For adolescents aged 12 to 17 years, the same dose escalation schedule as for adults should be applied.  It is recommended to regularly review the goals of treatment with semaglutide, particularly once the target weight (eg, BMI <85th percentile) has been achieved.

Treatment discontinuation criteria: Re-evaluate and discontinue treatment if the adolescent has not reduced their BMI by ≥ 5% after 12 weeks on the 2.4 mg dose (or maximum tolerated dose)

In the STEP TEENS trial, the mean change in BMI from baseline to week 68 was −16.1% (semaglutide) and 0.6% (placebo) with placebo (estimated difference, −16.7 percentage points; 95% confidence interval [CI], −20.3 to −13.2; P<0.001), an average of 18kg.  At week 68, 73% in the semaglutide group had weight loss of 5% or more,  compared with 18% in the placebo group.  

The incidence of gastrointestinal adverse events was 62% in the semaglutide group, compared with 42% (placebo).  Five participants in the semaglutide group (4%) developed cholelithiasis, with serious adverse events reported in 11% of semaglutide participants compared with 9% (placebo)⁶.

• Dose escalation should be delayed if significant gastrointestinal side effects occur.
• If a dose is not tolerated, consider reducing to the previous tolerated dose. 
• Re-escalation may be attempted once symptoms resolve.

• Screen for past or present history of disordered eating behaviour
• Personal or family history of medullary thyroid carcinoma (MTC) (data from rodents)
• Multiple endocrine neoplasia syndrome type 2 (MEN2)
• Prior idiopathic pancreatitis
• Pregnancy or planning pregnancy.  Current advice is to stop Wegovy 2 months before trying to conceive due to the long half-life and potential teratogenicity in animal studies.
• Lactation
• Congestive heart failure (NYHA) class IV
• Inflammatory bowel disease
• Diabetic gastroparesis
• Age ≥85 years. 

Counselling, awareness of red flag symptoms and setting appropriate expectations at treatment initiation are important parts of prescribing.  

Gastrointestinal events led to permanent treatment discontinuation in 4.3% of patients in the STEP trial⁴.

Most frequent during dose escalation; usually mild-to-moderate and transient.

(From Wegovy® New Zealand Data Sheet.)

Other GI effects, including bloating, belching, flatulence, GORD, haemorrhoids, and hiccups, may be reported.

• Hair loss (alopecia) – ~3% vs 1% placebo; more frequent with ≥20% weight loss; often mild and reversible.
• Cholelithiasis – 1.6% vs 0.7% placebo.
• Cholecystitis – 0.6% vs 0.2% placebo.
• Urolithiasis 
• Fracture risk – Female patients: 1% vs 0.2% placebo; ≥75 y: 2.4% vs 0.6% placebo.
• Increased heart rate – Mean rise ~1–4 bpm; monitor if symptomatic.
• Acute pancreatitis – ~0.2 cases/100 patient-years vs <0.1/100 patient-years placebo; advise urgent review for persistent severe abdominal pain.
• Appendicitis – 0.5% vs 0.2% placebo.
• Gastroparesis / Severe GI motility disorders – >2× risk vs comparator drugs; can present with persistent nausea, vomiting, abdominal distension, early satiety.
• Intestinal obstruction / Ileus – Reported post-market and in pharmacovigilance datasets; presents with severe abdominal pain, inability to pass stool/gas, vomiting.
• Dry mouth / altered taste ("Ozempic mouth") 

Gastrointestinal adverse effects, dizziness and dehydration

• There is a risk of dehydration leading to renal impairment, especially during dose escalation.
• Patients should be advised to maintain adequate fluid intake.
• There have been post-marketing reports of acute kidney injury and worsening of chronic renal failure, which have, in some cases, required hemodialysis.
• Patients with moderate renal impairment (eGFR ≥30 mL/min/1.73 m²) may experience more GI events
• Avoid in patients with severe inflammatory bowel disease or gastroparesis due to increased risk of GI symptoms.
• Dizziness can be experienced mainly during the dose escalation period. Driving or use of machines should be done cautiously if dizziness occurs.

Pancreatitis

• Acute pancreatitis has been reported. 
• 0.2 cases/100 patient-years vs <0.1/100 patient-years placebo
• Educate all patients on signs and symptoms (eg, persistent severe abdominal pain, nausea, vomiting).
• Discontinue permanently if pancreatitis is confirmed.
• Avoid in patients with a history of pancreatitis.
• A history of gallstone disease, lower BMI ≤30, previous acute pancreatitis, cardiovascular disease, and tobacco use have been associated with acute pancreatitis after initiation of GLP-1RA for obesity treatment⁷. 

Anaesthesia/sedation

• Use with caution due to risk of aspiration secondary to delayed gastric emptying.

Ophthalmic complications

Post marketing surveillance has identified rare ophthalmic complications in non-diabetic patients receiving GLP-1 RA pharmacotherapy.  It is not clear whether the mechanism is a rapid improvement in glycaemic control or a toxic effect^8.  A causal relationship has not been established; however, patients should be advised to seek immediate medical attention if rapid changes in vision occur.  

• Non-arteritic anterior ischaemic optic neuropathy (NAION) – Sudden, painless vision loss has been reported, resulting in the EMA adding a warning in 2025.  Risk from observational data is estimated ≤1 in 10,000/year.  
• Neovascular age-related macular degeneration (AMD) – Small but measurable increase in incidence in GLP-1 RA users.
• Papillitis / retinal microvascular events – Rare case reports of acute vision changes (other than NAION).

Although Wegovy is not indicated for the treatment of patients with type 2 diabetes, some individuals receiving it may have co-existing or undiagnosed diabetes.

In patients with type 2 diabetes and pre-existing diabetic retinopathy, rapid improvement in glycaemic control may transiently worsen retinopathy.

Such patients should be enrolled in diabetic retinopathy screening programmes and advised to seek immediate medical attention if they experience sudden changes in vision, flashing lights, or new floaters.
 

Warfarin

• Cases of decreased INR have been reported during concomitant use. 
• Upon initiation, frequent monitoring of INR is recommended.

DPP-4 inhibitors (eg. vildagliptin)

• Stop DPP-4 inhibitors before initiating a GLP-1 receptor agonist.
• Co-administration is not recommended due to limited additive benefit and increased risk of adverse effects.

Children

• The safety and efficacy of Wegovy in children below 12 years of age have not been studied.

Renal impairment

• Safe with mild to moderate kidney impairment eGFR 30-49 mL/min
• Patients should be educated to ensure adequate hydration.  
• Key point: Clinicians should consider monitoring renal function in patients with established CKD.  
• Patients with moderate renal impairment (eGFR ≥30) may experience more gastrointestinal effects.  
• There have been post-marketing reports of acute kidney injury and worsening of chronic renal failure, which have, in some cases, required haemodialysis.  
• Experience with use in severe renal impairment eGFR <30 mL/min is limited; caution is advised.  Not recommended for use in patients with end-stage renal disease. 

Hepatic impairment

• Safe in mild to moderate hepatic impairment (Child-Pugh score 5-9).  
• Specialist advice should be sought before using in patients with more severe hepatic disease.  

Diabetes

• Hypoglycaemia is not expected with Wegovy monotherapy, but may occur when used concomitantly with insulin or sulfonylureas; dose reduction of these agents may be required. In insulin-treated patients, avoid rapid or excessive insulin dose reduction, as this may increase the risk of diabetic ketoacidosis.

This MedCase was created by Dr Danuta Amelung, BHB, MbChB, FRNZCGP, AFRACMA, Dip. Paed, PGCertWHlth, PGDipTrvMed with expert review by Dr James Shand, Endocrinologist.